Additional capecitabine use in early-stage triple negative breast cancer patients receiving standard chemotherapy: a new era? A meta-analysis of randomized controlled trials

Feng Ye, Lei Bian, Jiahuai Wen, Ping Yu, Na Li, Xiaoming Xie, Xi Wang, Feng Ye, Lei Bian, Jiahuai Wen, Ping Yu, Na Li, Xiaoming Xie, Xi Wang

Abstract

Background: The efficiency of capecitabine has been proven in early-stage triple negative breast cancer (eTNBC) with residue invasive tumor (non-pCR) after standard neoadjuvant chemotherapy (NACT). However, for those unselected eTNBC patients without screening from NACT (i.e., newly diagnosed eTNBC patients undergoing breast surgery followed by adjuvant systemic therapy), the value of capecitabine has still remains unclear. We performed a meta-analysis of randomized controlled trials (RCTs) to evaluate whether additional capecitabine in eTNBC patients could improve clinical outcomes.

Methods: Seven RCTs (USO 01062, FinXX, GEICAM/2003, CREATE-X, CIBOMA/2004, CBCSG-010 and SYSUCC-001) were identified in online databases until December 2020 and included in the meta-analysis. We extracted the survival data including disease/relapse-free survival (DFS/RFS) and overall survival (OS), and utilized the STATA software to calculate the summarized hazard ratios (HRs) and 95% confidence intervals (95%CIs).

Results: A total of 3329 eTNBC patients were enrolled in this meta-analysis, with 1640 receiving standard neo-/adjuvant chemo-regimes alone, and the other 1689 receiving an additional capecitabine use, respectively. Both DFS and OS were significantly improved with the addition of capecitabine, and the benefits remained consistent in those unselected eTNBC patients without screening from NACT. Subgroup analysis further proved that this improvement in DFS was significant in both nodal negative and positive patients. Similar benefits are also found across menopausal status (both pre- and post-menopause). Regarding toxicity, the hand-foot syndrome and neutropenia are the most common capecitabine related adverse events, and are mostly tolerable.

Conclusions: The present meta-analysis of RCTs demonstrates for the first time that adding capecitabine to standard chemo-regimens could improve both DFS and OS in unselected eTNBC patients, and this benefit remains consistent regardless of nodal status and menopausal status, which may lead eTNBC therapy into a new era.

Keywords: Additional capecitabine; Meta-analysis; Standard chemotherapy; Survival; Triple negative breast cancer.

Conflict of interest statement

The authors declare to have no competing interest.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
The PRISMA flow diagram
Fig. 2
Fig. 2
Overall efficiency for additional Capecitabine use in early-staged TNBC. A summarized HR for OS in whole TNBC patients, all RCTs included; (B) summarized HR for DFS in whole TNBC patients, all RCTs included; (C) summarized HR for OS in unselected TNBC patients, with CREATE-X excluded; (D) summarized HR for DFS in unselected TNBC patients, with CREATE-X excluded
Fig. 3
Fig. 3
Subgroup analysis for additional Capecitabine use in early-staged TNBC. A summarized HR for DFS in unselected TNBC patients receiving A&T based regimens; (B) summarized HR for DFS in unselected TNBC patients with LN negative; (C) summarized HR for DFS in unselected TNBC patients with LN positive; (D) summarized HR for DFS in unselected TNBC patients with LN positive, capecitabine ≥6 cycles or 18 weeks; (E) summarized HR for DFS in unselected premenopausal TNBC patients; (F) summarized HR for DFS in unselected postmenopausal TNBC patients
Fig. 4
Fig. 4
A “NACT-guided mode” or a “Standard plus mode” in early-staged TNBC. A In a “NACT-guided mode”, early-staged TNBC patients with risk factors (i.e. T > 2 cm, or LN+, or young-onset (<40y), or high ki67 index) are recommended to receive standard NACT. After screening of NACT, patients with residual invasive tumor are strong candidates for additional 6–8 cycles capecitabine use. B In a “Standard plus mode”, standard CT plus capecitabine could be recommended to all early-staged TNBC patients with risk factors, according to the present evidences. For T1b-cN0M0 patients, additional capecitabine could also be considered and discussed with patients

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